Other signal transduction intermediates within the bone metabolism signaling pathways are being targeted by investigational therapies. One of these molecular targets is receptor activator of nuclear factor-kappaB ligand (RANKL), which drives osteoclast differentiation and activation (20). Denosumab (AMG 162) is a fully human anti-RANKL monoclonal antibody (33). This agent has primarily been investigated for the management of postmenopausal osteoporosis, in which it has been shown to increase bone mineral density and reduce bone turnover in women with low bone mineral density (34). In a 24-week study evaluating the efficacy and safety of denosumab in women with bone metastases from breast cancer (N = 255), the efficacy of denosumab in reducing the risk of SREs was not significantly different from that of IV bisphosphonates (35). Further studies are warranted to assess the activity of denosumab alone or in combination with bisphosphonates for the treatment of bone metastases from breast cancer.
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